Dimethylformamide → 1-(2-methoxy-4-(2,2,2-trifluoroethoxy)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

HRID 1473572Notes

Reaction equation

HRID 1473572 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([N:21](CC4C=CC(OC)=CC=4)[C:22]4[CH:27]=[CH:26][N:25]=[CH:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([O:37][CH3:38])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.FC(F)(F)S(O[CH2:56][C:57]([F:60])([F:59])[F:58])(=O)=O>O>[CH3:38][O:37][C:4]1[CH:3]=[C:2]([O:1][CH2:56][C:57]([F:60])([F:59])[F:58])[CH:7]=[CH:6][C:5]=1[C:8]1[C:17]2[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][N:23]=3)(=[O:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10][N:9]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 1364090681-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide

Product 1

HCID 866876331-(2-methoxy-4-(2,2,2-trifluoroethoxy)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamideYield 65.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A vial was charged with 1-(4-hydroxy-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (from EXAMPLE 361, STEP 1; 54 mg, 0.102 mmol), cesium carbonate (100 mg, 0.306 mmol), and DMF (511 μl). 2,2,2-Trifluoroethyl trifluoromethanesulfonate (28.0 μl, 0.204 mmol) was added and the vial was heated to 50° C. for 1 h. The mixture was diluted with water and extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was dissolved in DCM (1 mL) and TFA (1 mL), and the resulting solution was stirred overnight. The mixture was diluted with MeOH and concentrated. The residue was dissolved in EtOAc and washed with saturated aq. sodium bicarbonate solution. The aq. wash was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (3.5% MeOH/DCM) to give 1-(2-methoxy-4-(2,2,2-trifluoroethoxy)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (32.7 mg, 0.067 mmol, 65.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.06 (br. s., 1H), 8.70-8.61 (m, 2H), 8.57 (s, 1H), 8.25 (d, J=5.6 Hz, 1H), 8.06 (d, J=5.8 Hz, 1H), 7.94 (dd, J=1.9, 8.9 Hz, 1H), 7.72 (d, J=8.9 Hz, 1H), 7.30 (d, J=8.3 Hz, 1H), 7.03 (d, J=5.1 Hz, 1H), 6.90 (d, J=2.3 Hz, 1H), 6.82 (dd, J=2.3, 8.4 Hz, 1H), 4.89 (q, J=8.9 Hz, 2H), 3.65 (s, 3H). m/z (ESI) 491.2 (M+H)+.

Workup

  1. extractionextracted with EtOAc (3×)
  2. concentrationThe combined organic extracts were concentrated
  3. dissolutionThe residue was dissolved in DCM (1 mL)
  4. additionThe mixture was diluted with MeOH
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with saturated aq. sodium bicarbonate solution
  8. washThe aq. wash
  9. extractionwas extracted with EtOAc (2×)
  10. dry with materialThe combined organic extracts were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by chromatography on silica gel (3.5% MeOH/DCM)

Sources & evidence

ORD record
ord-2bb1206d06b743fd8b961b7eb4f93cfe
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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